Michael McConnell Associate Professor of the Practice

Antibiotic Resistance and Vaccine Development
Michael McConnell

Research Interests:

My current research focuses on using molecular approaches together with in vivo infection models to identify targets for the development of novel vaccines and therapeutics for antibiotic resistant infections. We are inspired by the idea that elucidating fundamental aspects of pathogen biology will allow us to gain insights that facilitate the development of new therapies.

Multidrug resistant bacterial species, such as Acinetobacter baumannii and Klebsiella pneumoniae, have been classified as “Critical Priority Pathogens” by the World Health Organization due to the global dissemination of strains with resistance to multiple antibiotic classes. My primary research interest in this area is the identification and molecular characterization of bacterial factors that can serve as targets for the development of novel vaccines and therapies. Our group employs A. baumannii and K. pneumoniae as model microorganisms for therapeutic target identification in Gram-negative species. We use whole genome mutagenesis techniques and whole organism transcriptional profiling (e.g. RNA-seq) to identify bacterial factors that participate in infection and contribute to antibiotic resistance. We have a particular interest in the elucidation of antigens that can be employed in vaccine design, and their characterization in experimental infection models. Our group has employed genetic, proteomic, and computational approaches to identify multiple bacterial components for vaccine design (lipopolysaccharide, porins, and siderophore receptors, among others), and has experimentally validated these components as vaccine antigens in murine models. Our work in this area has also focused on technologies that will facilitate the development of vaccines for multidrug resistant infections, such as outer membrane vesicles, nucleic acid-based vaccines, and genetically attenuated vaccines.

My teaching focuses on engaging students to promote critical thinking skills in both classroom and laboratory settings. I enjoy drawing from my own research to provide authentic research experiences to undergraduate students at early career stages to promote the development of laboratory and problem-solving skills.

Biography:

  • Associate Professor of the Practice, Department of Biological Sciences, University of Notre Dame, 2023-present
  • Associate Professor, National Centre for Microbiology, Madrid, 2018-2023
  • Research Faculty, Biomedical Institute of Seville, 2012-2018
  • Postdoctoral Fellow, Biomedical Institute of Seville, 2009-2011
  • M.D. University of Michigan Medical School, 2009
  • Ph.D. Microbiology and Immunology, University of Michigan, 2009
  • B.S. Biochemistry, University of Notre Dame, 2001

Selected Publications:

  • Tajuelo A, Carretero O, García-Ríos E, López-Siles M, Cano O, Vázquez M, Más V, Rodríguez-Goncer I, Lalueza A, López-Medrano F, Juan RS, Fernández-Ruiz M, Aguado JM, McConnell M.J.*, Pérez-Romero P. Virus-Specific Humoral Immunity at Admission Predicts the Development of Respiratory Failure in Unvaccinated SARS-CoV-2 Patients. Frontiers in Immunology. (2022) Apr 25;13:878812.
  • Prieto Martin Gil S, Tajuelo A, López-Siles M, McConnell, M.J.* Subinhibitory Concentrations of Clinically-Relevant Antimicrobials Affect Resistance-Nodulation-Division Family Promoter Activity in Acinetobacter baumannii. Front Microbiol. (2021);12:780201.
  • Olmeda-López H, Corral-Lugo A, McConnell, M.J.* Effect of Subinhibitory Concentrations of Antibiotics and Disinfectants on ISAba-Mediated Inactivation of Lipooligosaccharide Biosynthesis Genes in Acinetobacter baumannii. Antibiotics. (2021);10:1259.
  • López-Siles M, Corral-Lugo A, McConnell, M.J.* Vaccines for multidrug resistant Gram negative bacteria: lessons from the past for guiding future success. FEMS Microbiol Rev. (2021) 5;45(3):fuaa054.
  • McConnell, M.J.* and Martín-Galiano AJ. Designing multi-antigen vaccines against Acinetobacter baumannii using systemic approaches. Front Immunol. (2021) Apr 16;12:666742.
  • Vinuesa V, Cruces R, Nonnoi F, McConnell, M.J.* Inhibition of LpxC increases the activity of iron chelators and gallium nitrate in multidrug-resistant Acinetobacter baumannii. Antibiotics. (2021) 20;10:609
  • Vinuesa V, McConnell, M.J.* Recent advances in iron chelation and gallium-based therapies for antibiotic resistant bacterial infections. Int J Mol Sci. (2021) 12;22:2876.
  • Corral-Lugo, A., López-Siles, M., López, D., McConnell, M.J.*, Martin-Galiano, A.J.* Identification and analysis of unstructured, linear B-cell epitopes in SARS-CoV-2 virion proteins for vaccine development. (2020) Vaccines, 8 (3), art. no. 397, pp. 1-21.
  • Pulido, M.R., García-Quintanilla, M., Pachón, J., McConnell, M.J.* A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection. (2020) Vaccine, 38 (4), pp. 719-724.